Rational design, synthesis, and structure-activity relationships of 5-amino-1H-pyrazole-4-carboxylic acid derivatives as protein tyrosine phosphatase 1B inhibitors

Bioorg Med Chem. 2017 Jan 1;25(1):67-74. doi: 10.1016/j.bmc.2016.10.012. Epub 2016 Oct 11.

Abstract

A series of novel amino-carboxylic based pyrazole as protein tyrosine phosphatase 1B (PTP1B) inhibitors were designed on the basis of structure-based pharmacophore model and molecular docking. Compounds containing different hydrophobic tail (1,2-diphenyl ethanone, oxdiadizole and dibenzyl amines) were synthesized and evaluated in PTP1B enzymatic assay. Structure-activity relationship based optimization resulted in identification of several potent, metabolically stable and cell permeable PTP1B inhibitors.

Keywords: Hydrophobic; Oxadiazole; Permeability; Pharmacophore; Protein tyrosine phosphatase 1B.

MeSH terms

  • Amination
  • Carboxylic Acids / chemistry
  • Carboxylic Acids / pharmacology
  • Drug Design
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Molecular Docking Simulation
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
  • Pyrazoles / chemistry*
  • Pyrazoles / pharmacology*

Substances

  • Carboxylic Acids
  • Enzyme Inhibitors
  • Pyrazoles
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1